JPH0729965B2 - Process for producing 1-alkoxy-2-methylnaphthalene - Google Patents

Description

Description: FIELD OF THE INVENTION The present invention relates to a novel process for producing 1-alkoxy-2-methylnaphthalene. More specifically, the present invention relates to a method for producing 1-alkoxy-2-methylnaphthalene, which comprises reacting 1-halogeno-2-methylnaphthalene in dimethylformamide with an alkali metal alkoxide in the presence of a copper catalyst.

1-Alkoxy-2-methylnaphthalene, which is the object of the present invention, is useful as an intermediate for medicines such as vitamin K, or as a synthetic raw material for dyes, photographic sensitizers and the like.

BACKGROUND ART As a method for producing 1-alkoxy-2-methylnaphthalene, a method using 2-methyl-1-naphthol as a raw material has been known. For example, JCMadelmont et al. Have reacted 2-methyl-1-naphthol with methyl iodide in water-acetone at 60 ° C for 12 hours to collect 1-methoxy-2-methylnaphthalene. 70%
Obtained at [Journal, Of, Labeled, Compounds, And, Radio Pharmaceuticals (Journal
of Labeled Compounds and Radiopharmaceuticals), 1
4, (2), 281-91 (1978)]. However, the above method has drawbacks such that the starting material, 2-methyl-1-naphthol, is unstable to air and heat and is expensive, and the yield of the target product is about 70%. But I'm not satisfied.

Description of the present invention The present inventors have conducted various studies on a method for producing 1-alkoxy-2-methylnaphthalene, which eliminates the drawbacks of the conventional method, is easy to operate, and is economical in a good yield. The present invention has been completed, knowing that the intended purpose can be achieved by reacting 1-halogeno-2-methylnaphthalene with an alkali metal alkoxide.

Therefore, the present invention uses 1-halogeno-2-methylnaphthalene as a raw material, and uses it as a starting material in dimethylformamide.
It is a method for producing 1-alkoxy-2-methylnaphthalene which is reacted with an alkali metal alkoxide in the presence of a copper catalyst.

The starting material 1-halogeno-2-methylnaphthalene of the present invention can be easily obtained by a known method. For example, 1-bromo-2-methylnaphthalene can be easily obtained by adding bromine (Br ₂ ) dropwise to a solution of 2-methylnaphthalene at low temperature.

Examples of the copper catalyst used in the present invention include cuprous iodide, cuprous iodide, cuprous chloride, cupric chloride, and other halogenated copper, and cuprous oxide.
Examples of alkali metal alkoxides include sodium methoxide, sodium ethoxide, potassium methoxide, potassium ethoxide, and the like. The alkali metal alkoxide can be used as such (solid form) or in the form of a solution in a suitable solvent, preferably an alcohol solvent. In the present invention, dimethylformamide is used as the solvent. The reaction usually proceeds at 60 to 150 ℃, but 85 to 1 to obtain high yield.
Particularly preferred is 10 ° C.

After completion of the reaction, the target 1-alkoxy-2-methylnaphthalene can be separated and purified easily by a conventional method such as extraction with an organic solvent, concentration, distillation, chromatography and the like.

According to the present invention, the objective 1-alkoxy-2 can be performed with a simple operation.
-Methylnaphthalene can be obtained in high yields of 90% or more.

The invention is further described in the following examples.

Example 1 Preparation of 1-methoxy-2-methylnaphthalene Equipped with dropping funnel, reflux condenser, thermometer, and stirrer
To a 1-liter four-necked round-bottomed flask, 221.4 g (1 mol, 90% purity) of 1-bromo-2-methylnaphthalene, 19.1 g of cuprous iodide, and 200 ml of dimethylformamide were sequentially charged. The resulting reaction mixture was heated and stirred, and at an internal temperature of about 85 ° C, 232.2 g (1.2 mol) of sodium methoxide (28% methanol solution)
Was added dropwise over about 1 hour. The reaction mixture was stirred for about 2 hours while distilling off the solvent methanol to keep the reaction temperature around 95 ° C. High Performance Liquid Chromatography (HPL
The reaction was completed when the raw material 1-bromo-2-methylnaphthalene disappeared due to C).

The reaction mixture (40-50 ° C) was depressurized to remove insoluble materials (NaBr, cuprous iodide, etc.), and the mixture was mixed with 300 ml of hexane each time.
It was extracted twice, and 200m of water was added to the lower dimethylformamide layer.
l was added and extracted with 300 ml of hexane. The hexane layers were combined, washed twice with 300 ml each of dilute hydrochloric acid and 300 ml of water, then washed with 300 ml of saturated saline until neutral, dried over anhydrous sodium sulfate, and concentrated. Thus, 170.3 g of a brown oily residue was obtained. This was purified by silica gel column chromatography (eluent: hexane / dichloromethane = 10: 1) to obtain 149 g of the title compound (yield 97%; purity 98%) as a colorless oil. The structure was confirmed by NMR, IR and MS.

Example 2 Equipped with dropping funnel, reflux condenser, thermometer, and stirrer
In a 200 ml four-necked round bottom flask, 1-bromo-2-methylnaphthalene 11.1 g (0.05 mol, 9% purity), cupric chloride 0.7 g
(0.005 mol) and 10 ml of dimethylformamide were sequentially charged. The resulting reaction mixture was heated and stirred, and at an internal temperature of 80 ° C, sodium methoxide (28% methanol solution) 11.6
g (0.06 mol) was added dropwise over 30 minutes. The reaction mixture was heated and stirred for 12 hours while distilling methanol so that the internal temperature was kept at 80 to 100 ° C.

Then, a separation operation was carried out in the same manner as in Example 1 to obtain 8.6 g of a brown oily residue, which was further purified by silica gel column chromatography (eluent: hexane / dichloromethane = 10: 1) to obtain the desired product 1-methoxy-2-. Methylnaphthalene 7.
5 g (yield 97%; purity 97%) was obtained.

Example 3 Example 2 was repeated except that 11.6 g (0.12 mol) of cuprous chloride was used in place of cupric chloride and heating and stirring were performed for 5 hours.
In the same manner as above, 8.4 g of a brown oily residue was obtained, which was further purified by silica gel column chromatography to give 7.3 g of the desired product 1-methoxy-2-methylnaphthalene (yield 95%;
Purity 97%) was obtained.

Example 4 The procedure of Example 2 was repeated except that 0.73 g (0.005 mol) of cuprous oxide was used in place of cupric chloride to obtain 8.3 g of a brown oily residue. Further purify by silica gel column chromatography to obtain the desired product 1-
Methoxy-2-methylnaphthalene 7.0 g (yield 91%; purity
97%).

Example 5 20 equipped with dropping funnel, reflux condenser, thermometer and stirrer
In a 0 ml round bottom flask, 1.4 g (0.06 mol) of small pieces of metallic sodium were added to 40 ml of ethanol and stirred. After the sodium metal is completely dissolved in ethanol, cuprous iodide
0.95 g (0.005 mol) and 10 ml of dimethylformamide were added. The resulting reaction mixture was heated and stirred, and at an internal temperature of 80 ° C, 11.1 g of 1-bromo-2-methylnaphthalene (0.05 m
ol, 90% purity) was added dropwise over about 30 minutes. The reaction mixture was stirred for 12 hours while distilling ethanol so that the internal temperature was kept at 80 to 100 ° C.

Then, the reaction solution was passed under reduced pressure to remove insolubles, the solution was extracted twice with 100 ml of hexane each time, 100 ml of water was added to the lower layer (dimethylformamide layer), and the mixture was extracted with 100 ml of hexane. Combine hexane extracts, dilute hydrochloric acid 100 ml, water 100 ml
Each time, the mixture was washed twice with 100 ml of saturated saline until neutral, dried over anhydrous sodium sulfate, and concentrated to obtain 9.3 g of a brown oily residue. Silica gel column chromatography (eluent: hexane / dichloromethane = 1)
After purification by 0: 1), 7.9 g of the desired product 1-ethoxy-2-methylnaphthalene (yield 94%, purity 96%) was obtained in the form of a colorless viscous oil. This product solidified when left standing.

 ─────────────────────────────────────────────────── ─── Continuation of the front page (56) References JP-A-62-106029 (JP, A) “Chemical Society of Japan, New Experimental Chemistry, Volume 14, Synthesis and Reactions of Organic Compounds (I)” (SHO 52- 11-20) Maruzen P. 571. J. Chem. Soc. , (C), 1969 P.P. 312-P. 315

Claims (4)

[Claims] 1. A 1-halogeno-2-methylnaphthalene,
A method for producing 1-alkoxy-2-methylnaphthalene, which comprises reacting with an alkali metal alkoxide in the presence of a single copper catalyst in dimethylformamide. 2. A 1-halogeno-2-methylnaphthalene,
A method according to claim 1 which is 1-bromo-2-methylnaphthalene. 3. A process according to claim 1 in which the alkali metal alkoxide is sodium methoxide or sodium ethoxide. 4. A process according to claim 1 wherein the copper catalyst is selected from cuprous iodide, cuprous oxalate, cuprous chloride, cupric chloride and cuprous oxide.